PB2024: PREVALENCE OF TYPE 1 GAUCHER DISEASE IN PATIENTS WITH MULTIPLE MYELOMA: FIRST INTERIM ANALYSIS OF A PROSPECTIVE, MULTICENTER, OBSERVATIONAL STUDY
Authors: M. Offidani, C. Zizzo, S. Rupoli, I. Federici, A. Bossi, S. Morè, V. M. Manieri, M. T. Petrucci, T. Caravita di Toritto, M. Brunori, A. Gozzetti, A. Tordi, F. Fazio, C. Lisi, E. Morsia, L. Corvatta, A. Olivieri, G. Duro
Journal: HemaSphere (2022)

Background: Type I Gaucher disease (GD1) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, that degrades glycosphingolipids. In GD1, aberrant macrophage activation and immune dysregulation are associated with increased cancer risk. The association of GD1 and cancer was examined in the International Collaborative Gaucher Group (ICGG) Registry comprising 2,742 eligible patients [Rosenbloom BE et al, 2005]. This study found no increase of overall cancer risk (0.79, 95% CI 0.67–0.94). Nevertheless, there was a 5.9-fold (95% CI 2.8–10.8) increased risk of Multiple Myeloma (MM). However, cancer risk was likely underestimated in this study because the younger age distribution of the study population and incomplete ascertainment because the ICGG is an observational registry to track responses to treatment (ClinicalTrails.gov NCT 00358943). Therefore, we thought it was useful to prospectively investigate the prevalence of GD1 in a large population of patients affected by MM Aims: The primary objective of this study was to determine the prevalence of Dried Blood Spots (DBS) test positivity in a large prospective MM population. Patients with DBS test positivity were then purposed for genetic test to confirm the diagnosis GD1. If the observed prevalence will be significantly higher than predicted, the identification of potential risk predictors in the selected population will be carried out Methods: This is an observational, prospective, cross-sectional, multicenter study. Considering that no data are available about the effective prevalence of GD1 in patients affected by MM, the sample size has been determined considering clinically relevant a prevalence of the condition > 0.5% for defining as “high risk” the selected population. To test this hypothesis with an alpha error of 5% and a statistical power of 95%, we will enroll approximately 1000 patients in 46 hematology centers overall. All patients, according to the inclusion criteria and provided a signed written informed consent, with a confirmed diagnosis of MM will be screened for GD1 undertake through DBS sampling technique. The DBS test will be centralized at the Istituto per la Ricerca e l’Innovazione Biomedica CNR-Palermo. This is the first interim analysis planned when the first posivity DBS test was happened Results: Two hundred and sixty-eight patients were enrolled, so far. Median age was 67 years (range 37-90) and 58% of patients were male. No patients was of Jew etnicity, one was asiatic and one was black, Caucasian the remaining. Fifty-eight percent had newly diagnosed MM while 42% had relapsed-refractory MM. SMM or MM was diagnosed in 10% and 90% of patients, respectively. Monoclonal component was IgG in 54%, IgA in 25%, light chain in 11%. Median Ferritin was 322 ng/ml (range 17-1236) and median Alkaline Phosphatase was 81 U/L (range 29-355). Data of DBS test found with mutations in GBA gene, were pictured in the Table 1. DBS test was considered positive in 1 patient; so the prevalence was 1/268 (0.4%), so far. Image:Summary/Conclusion: Despite the trial enrolment is just in the first quarter of the whole planned sample size, our preliminary data showed an interesting prevalence of DBS test positivity (0.4%). Data updates are needed to define the real incidence of DBS test positivity in MM. Likewise, pathological genetic test in DBS positive patients is needed to confirm the diagnosis of GD1 and to demonstrate the relationship of this disease and plasma cell disorders.